Tuberculosis: A persistent threat, yet clinical trials show promise
Researchers at The Institute advance the search for preventive treatments for multidrug-resistant TB
In Montreal, cases of tuberculosis (TB) have increased by 54% in 2024 compared to the average from 2010 to 2023, according to a recent call for vigilance issued by Montreal’s public health department, reminding us that even in low-incidence countries, the disease remains an important threat, exacerbated by multidrug-resistant (MDR) TB.
The results of the VQUIN MDR clinical trial conducted by a team from the University of Sydney in collaboration with Dick Menzies, Marcel Behr, Andrea Benedetti and graduate student Ori Solomon from the Research Institute of the McGill University Health Centre (The Institute) show that the antibiotic levofloxacin could be used safely to prevent multidrug-resistant TB. These results, recently published in the New England Journal of Medicine, offer a glimmer of hope for reversing the spread of TB worldwide.
“Caused by bacteria resistant to rifampicin and isoniazid—the drugs commonly used to prevent the onset of the disease and the spread of infection—multidrug-resistant TB affects an estimated 400,000 people worldwide each year, according to the World Health Organization,” says Dr. Marcel Behr, Senior Scientist in the Infectious Diseases and Immunity in Global Health Program at The Institute and Director of the Division of Infectious Diseases at the McGill University Health Centre. “Without a safe and effective treatment, these people may progress to clinical disease and potentially transmit these resistant forms to others.”
This trial, led by Gregory Fox, Director of the Australian National Health and Medical Research Council Centre for Research Excellence in Tuberculosis at the University of Sydney, was a randomized, double-blind, controlled trial in which participants living with individuals infected with MDR TB received either a daily oral dose of levofloxacin or a placebo for 6 months. It was conducted across 10 provinces in Vietnam, a country with a high rate of drug-resistant TB, and found that levofloxacin reduced the risk of MDR-TB in adults and adolescents by 45 percent.
During the 30-month follow-up period, TB developed in 6 of the 1023 participants who received levofloxacin and in 11 of the 1018 participants who received a placebo. There was little difference in serious adverse events between the two groups, but mild adverse events were more common with levofloxacin.
“The study addressed an important question: the long-term safety of taking this antibiotic, levofloxacin, for six months. Fortunately, it was well tolerated and not associated with any major adverse effects,” explains Ori Solomon, who sequenced the
genomes of the bacteria from patients with MDR TB and their contacts who went on to develop TB, to determine whether new mutations in their strains had been induced by the use of the antibiotic. “We also found no new acquired resistance to the antibiotic. Together, this shows the treatment is both safe to the patient and poses a low risk of driving antibiotic resistance in TB.”
Although levofloxacin almost halved the risk of MDR-TB in the trial, the study authors note that the difference was not statistically significant, on its own. However, they explain that the incidence of TB was also decreased by levofloxacin in a separate, independent study, called TB-CHAMP, done in South Africa and published in the same issue.
Together, the two studies demonstrated that levofloxacin can stop the risk of MDR-TB among family and other household members, curtailing the global impact of this dangerous pathogen. As highlighted in an accompanying editorial, a meta-analysis of individual patient data from the two trials “showed that levofloxacin led to a relative reduction of approximately 60% in the cumulative incidence of tuberculosis as compared with placebo.”
For more information, read the press release.
About the study
The study Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis in Vietnam was conducted by Greg J. Fox, Nguyen Viet Nhung, Nguyen Cam Binh, Nguyen Binh Hoa, Frances L. Garden, Andrea Benedetti, Pham Ngoc Yen, Nguyen Kim Cuong, Emily L. MacLean, Manisha Yapa, David W. Dowdy, Nguyen Huu Lan, Elyse Guevara-Rattray, Pham Duc Cuong, Ori Solomon, Marcel A. Behr, Ben J. Marais, Steven M. Graham, Dick Menzies, Nguyen Thu Anh and Guy B. Marks.
DOI: 10.1056/NEJMoa23143
The VQUIN trial was funded by the Australian National Health and Medical Research Council (NHMRC). It was sponsored by the Woolcock Institute of Medical Research, and implemented in partnership with the Vietnam National Tuberculosis Program.